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Driver mutations lung cancer

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https://www.readbyqxmd.com/read/29666949/precision-medicine-against-alk-positive-non-small-cell-lung-cancer-beyond-crizotinib
#1
REVIEW
Biagio Ricciuti, Andrea De Giglio, Carmen Mecca, Cataldo Arcuri, Sabrina Marini, Giulio Metro, Sara Baglivo, Angelo Sidoni, Guido Bellezza, Lucio Crinò, Rita Chiari
Anaplastic lymphoma kinase (ALK) rearrangements represent the molecular driver of a subset of non-small cell lung cancers (NSCLCs). Despite the initial response, virtually all ALK-positive patients develop an acquired resistance to the ALK inhibitor crizotinib, usually within 12 months. Several next-generation ALK inhibitors have been developed in order to overcome crizotinib limitation, providing an unprecedented survival for this subset of patients. The aim of this review to summarize the current knowledge on ALK tyrosine kinase inhibitors (TKIs) in the treatment of advanced ALK-positive NSCLC, focusing on the role of novel ALK inhibitors in this setting...
April 17, 2018: Medical Oncology
https://www.readbyqxmd.com/read/29662630/type-ii-raf-inhibitor-causes-superior-erk-pathway-suppression-compared-to-type-i-raf-inhibitor-in-cells-expressing-different-braf-mutant-types-recurrently-found-in-lung-cancer
#2
Amir Noeparast, Philippe Giron, Sylvia De Brakeleer, Carolien Eggermont, Ulrike De Ridder, Erik Teugels, Jacques De Grève
A large fraction of somatic driver BRAF mutations in lung cancer are non-V600 and impaired-kinase. Non-V600 BRAF mutations predict sensitivity to combination of a type I RAF inhibitor, Dabrafenib, and a MEK inhibitor, Trametinib. Singly, Dabrafenib only weakly suppresses mutant BRAF-induced ERK signaling and can induce ERK paradoxical activation in CRAF-overexpressing cells. The present study compared the effects of Dabrafenib and a type II RAF inhibitor, AZ628, on ERK activity in HEK293T cells expressing several tumor-derived BRAF mutants, and in a non-V600 and impaired-kinase BRAF-mutant lung cancer cell line (H1666)...
March 23, 2018: Oncotarget
https://www.readbyqxmd.com/read/29657135/precision-targeted-therapy-with-blu-667-for-ret-driven-cancers
#3
Vivek Subbiah, Justin F Gainor, Rami Rahal, Jason D Brubaker, Joseph L Kim, Michelle Maynard, Wei Hu, Qiongfang Cao, Michael P Sheets, Douglas Wilson, Kevin J Wilson, Lucian DiPietro, Paul Fleming, Michael Palmer, Mimi I Hu, Lori Wirth, Marcia S Brose, Sai-Hong Ignatius Ou, Matthew Taylor, Elena Garralda, Stephen Miller, Beni Wolf, Christoph Lengauer, Timothy Guzi, Erica K Evans
The receptor tyrosine kinase, rearranged during transfection (RET), is an oncogenic driver activated in multiple cancers including non-small cell lung cancer (NSCLC), medullary thyroid cancer (MTC) and papillary thyroid cancer (PTC). No approved therapies have been designed to target RET; treatment has been limited to multi-kinase inhibitors (MKIs) which can have significant off-target toxicities and limited efficacy. BLU-667 is a highly potent and selective RET inhibitor designed to overcome these limitations...
April 15, 2018: Cancer Discovery
https://www.readbyqxmd.com/read/29656747/efficacy-and-safety-of-nivolumab-in-previously-treated-patients-with-non-small-cell-lung-cancer-a-multicenter-retrospective-cohort-study
#4
Daichi Fujimoto, Hiroshige Yoshioka, Yuki Kataoka, Takeshi Morimoto, Young Hak Kim, Keisuke Tomii, Tadashi Ishida, Masataka Hirabayashi, Satoshi Hara, Manabu Ishitoko, Yasushi Fukuda, Moon Hee Hwang, Naoki Sakai, Motonari Fukui, Hitoshi Nakaji, Mitsunori Morita, Tadashi Mio, Takehiro Yasuda, Takakazu Sugita, Toyohiro Hirai
INTRODUCTION: Nivolumab has been shown to be effective and safe in previously treated patients with advanced non-small cell lung cancer (NSCLC). However, little is known regarding its performance in real-world (i.e., non-trial) settings. Furthermore, nivolumab efficacy is unknown in patients who are ineligible for clinical trials or who are categorized into small subgroups in such trials. METHODS: We conducted a 15-center, observational, retrospective cohort study of patients with advanced NSCLC who received nivolumab monotherapy between January and December 2016...
May 2018: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/29650813/-the-cutting-edge-of-sarcoma-genomics
#5
Katsuhito Takahashi
Sarcoma is well-known rare cancer with few therapeutic options. Recent comprehensive genomic analyses of adult soft tissue sarcoma revealed few somatic mutations and massive copy number variations(CNVs)by the specific chromosomes. Those features are quite different from the genomics of carcinoma such as lung and colon cancers in which driver and passenger mutations play a central role in the pathogenesis. Furthermore, it has been demonstrated that substantial population of sarcoma patients has pathological germline variants of cancer predisposition genes...
April 2018: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/29650269/current-perspectives-on-the-crosstalk-between-lung-cancer-stem-cells-and-cancer-associated-fibroblasts
#6
REVIEW
Cristina Alguacil-Núñez, Inés Ferrer-Ortiz, Elena García-Verdú, Pilar López-Pirez, Irene Maria Llorente-Cortijo, Bruno Sainz
Lung cancer, in particular non-small cell lung carcinoma (NSCLC), is the second most common cancer in both men and women and the leading cause of cancer-related deaths worldwide. Its prognosis and diagnosis are determined by several driver mutations and diverse risk factors (e.g. smoking). While immunotherapy has proven effective in some patients, treatment of NSCLC using conventional chemotherapy is largely ineffective. The latter is believed to be due to the existence of a subpopulation of stem-like, highly tumorigenic and chemoresistant cells within the tumor population known as cancer stem cells (CSC)...
May 2018: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/29624782/a-molecular-pathological-study-of-four-cases-of-ciliated-muconodular-papillary-tumors-of-the-lung
#7
Toshiaki Kataoka, Koji Okudela, Mai Matsumura, Hideaki Mitsui, Takehisa Suzuki, Chihiro Koike, Tomoe Sawazumi, Shigeaki Umeda, Yoko Tateishi, Shoji Yamanaka, Yoshihiro Ishikawa, Hiromasa Arai, Michihiko Tajiri, Kenichi Ohashi
Ciliated muconodular papillary tumors (CMPTs) are a recently categorized benign or low-grade malignant neoplasm that develops in the peripheral lung. Only about 40 cases have been reported to date, and the clinicopathological characteristics have yet to be defined in detail. Here, we present four cases of CMPTs with a focus on their immunohistochemical profiles and driver gene mutations. These tumors were a papillary proliferation of a mixture of ciliated, mucous, and basal cells located in the peripheral lung...
April 6, 2018: Pathology International
https://www.readbyqxmd.com/read/29622080/targeted-therapy-and-immunotherapy-in-the-treatment-of-non-small-cell-lung-cancer
#8
REVIEW
Girish S Shroff, Patricia M de Groot, Vassiliki A Papadimitrakopoulou, Mylene T Truong, Brett W Carter
The treatment strategy in advanced non-small cell lung cancer (NSCLC) has evolved from empirical chemotherapy to a personalized approach based on histology and molecular markers of primary tumors. Targeted therapies are directed at the products of oncogenic driver mutations. Immunotherapy facilitates the recognition of cancer as foreign by the host immune system, stimulates the immune system, and alleviates the inhibition that allows the growth and spread of cancer cells. The authors describes the role of targeted therapy and immunotherapy in the treatment of NSCLC, patterns of disease present on imaging studies, and immune-related adverse events encountered with immunotherapy...
May 2018: Radiologic Clinics of North America
https://www.readbyqxmd.com/read/29608968/next-generation-sequencing-assisted-in-establishing-the-diagnosis-and-treatment-for-a-chinese-patient-with-breast-and-lung-multiple-primary-malignancies
#9
Chunqing Song, Zhengxing Gao, Jiabao Zong, Junping Shi, Ming Yao, Guilong Lu, Xiaoliang Liu, Kai Wang, Lei Han
INTRODUCTION: A case of primary lung cancer was reported, which was misdiagnosed as breast cancer metastasis to the lung based on pathology in combination with a history of breast cancer. METHODS: The common driver gene mutation was detected in different lesions by next generation sequencing (NGS), and it was shown that the genomic profiling of lung lesion and breast lesion were inconsistent. RESULTS: The typical driver mutation of EGFR L858R in lung cancer was found in lung lesion, and the patient received the first-generation EGFR-TKI, icotinib, as treatment and achieved a partial response...
March 30, 2018: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/29596910/intrinsic-and-extrinsic-regulation-of-pd-l2-expression-in-oncogene-driven-non-small-cell-lung-cancer
#10
Daisuke Shibahara, Kentaro Tanaka, Eiji Iwama, Naoki Kubo, Keiichi Ota, Koichi Azuma, Taishi Harada, Jiro Fujita, Yoichi Nakanishi, Isamu Okamoto
INTRODUCTION: The interaction of programmed cell death-ligand 2 (PD-L2) with programmed cell death-1 (PD-1) is implicated in tumor immune escape. The regulation of PD-L2 expression in tumor cells has remained unclear, however. We here examined intrinsic and extrinsic regulation of PD-L2 expression in non-small cell lung cancer (NSCLC). METHODS: PD-L2 expression was evaluated by reverse transcription and real-time polymerase chain reaction analysis and by flow cytometry...
March 26, 2018: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/29593887/immunotherapy-in-treatment-na%C3%A3-ve-advanced-non-small-cell-lung-cancer
#11
REVIEW
Vinicius Ernani, Apar Kishor Ganti
Lung cancer is the leading cause of cancer-related mortality worldwide. Non-small cell lung cancer (NSCLC) comprises approximately 85% of lung cancers and, unfortunately, more than half of these patients are diagnosed with metastatic disease. Platinum-based chemotherapy has for long been the standard frontline therapy for advanced disease. Despite remarkable advances in targeted therapy for a subset of patients harboring a driver mutation, the prognosis in the majority of the lung cancer population have not changed significantly...
February 2018: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/29587667/outcomes-of-pemetrexed-based-chemotherapies-in-her2-mutant-lung-cancers
#12
Yan Wang, Shijia Zhang, Fengying Wu, Jing Zhao, Xuefei Li, Chao Zhao, Shengxiang Ren, Caicun Zhou
BACKGROUND: HER2 mutation has been found to be an oncogenic driver gene in non-small cell lung cancers(NSCLC) and HER2-directed therapies have shown promising results in this unique population, while little is known about its association with outcomes of chemotherapy. The aim of this study was to investigate the efficacy of first line chemotherapy in patients with advanced HER2-mutant lung adenocarcinomas. METHODS: Patients with advanced NSCLC(N = 1714) initially underwent testing for EGFR, KRAS, BRAF mutations and ALK, ROS1 rearrangements, and negative cases were then assessed for HER2 mutations using the method of amplification refractory mutation system(ARMS)...
March 27, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29581811/lymphocyte-to-monocyte-ratio-and-modified-glasgow-prognostic-score-predict-prognosis-of-lung-adenocarcinoma-without-driver-mutation
#13
Seigo Minami, Shouichi Ihara, Sung-Ho Kim, Suguru Yamamoto, Kiyoshi Komuta
Background: Neutrophil to lymphocyte ratio (NLR), lymphocyte to monocyte ratio (LMR) and modified Glasgow prognostic score (mGPS) are useful prognostic markers based on host-related systemic inflammatory response. They have been shown as independent prognostic biomarkers in various cancers, including non-small cell lung cancer. However, there has been little evidence for a specific population of pulmonary adenocarcinoma without active epidermal growth factor receptor (EGFR) mutation. Methods: We retrospectively reviewed 159 patients who met the following criteria: histologically or cytologically diagnosed adenocarcinoma, confirmed wild-type EGFR, started first-line cytotoxic chemotherapy between July 2007 and March 2017 at our hospital, and c-stage IIIB or IV...
February 2018: World Journal of Oncology
https://www.readbyqxmd.com/read/29572000/pd-l1-expression-in-lung-adenocarcinoma-harboring-egfr-mutations-or-alk-rearrangements
#14
Yasuto Yoneshima, Kayo Ijichi, Satoshi Anai, Keiichi Ota, Kohei Otsubo, Eiji Iwama, Kentaro Tanaka, Yoshinao Oda, Yoichi Nakanishi, Isamu Okamoto
OBJECTIVES: Expression of programmed cell death-ligand 1 (PD-L1) has been associated with clinical outcome of programmed cell death-1 (PD-1) pathway blockade in non-small cell lung cancer (NSCLC). The PD-L1 IHC 22C3 pharmDx assay, the only companion diagnostic for pembrolizumab therapy, has revealed that ∼30% of all NSCLCs express PD-L1 at a high level. The frequency of high PD-L1 expression in NSCLCs with known driver oncogenes has remained unclear, however. MATERIALS AND METHODS: We retrospectively evaluated PD-L1 expression with the 22C3 assay in tumor tissue of 80 lung adenocarcinoma patients including 71 with EGFR mutations and 9 with ALK rearrangements, all of whom were treated with corresponding tyrosine kinase inhibitors (TKIs)...
April 2018: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/29570743/novel-putative-drivers-revealed-by-targeted-exome-sequencing-of-advanced-solid-tumors
#15
Antonio Pannuti, Aleksandra Filipovic, Chindo Hicks, Elliot Lefkowitz, Travis Ptacek, Justin Stebbing, Lucio Miele
Next generation sequencing (NGS) is becoming increasingly integrated into oncological practice and clinical research. NGS methods have also provided evidence for clonal evolution of cancers during disease progression and treatment. The number of variants associated with response to specific therapeutic agents keeps increasing. However, the identification of novel driver mutations as opposed to passenger (phenotypically silent or clinically irrelevant) mutations remains a major challenge. We conducted targeted exome sequencing of advanced solid tumors from 44 pre-treated patients with solid tumors including breast, colorectal and lung carcinomas, neuroendocrine tumors, sarcomas and others...
2018: PloS One
https://www.readbyqxmd.com/read/29567557/breaking-the-biomarker-code-pd-l1-expression-and-checkpoint-inhibition-in-advanced-nsclc
#16
REVIEW
B Melosky, Q Chu, R A Juergens, N Leighl, D Ionescu, M-S Tsao, D McLeod, V Hirsh
BACKGROUND: Lung cancer is the most common cause of cancer-related death among males and the second leading cause among females globally. Checkpoint inhibitors re-engage the immune system to fight cancer. This review evaluates phase III data on the use of checkpoint inhibitors in the treatment of advanced NSCLC and addresses PD-L1 expression in predicting efficacy. METHODS: Six phase III clinical trials investigating checkpoint inhibitors for NSCLC were identified through a search of PubMed (to November 15, 2016) and conference databases, with findings updated from a directed search of eligible studies conducted in January 2018...
February 22, 2018: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/29556275/sequencing-of-circulating-tumor-dna-for-dynamic-monitoring-of-gene-mutations-in-advanced-non-small-cell-lung-cancer
#17
Ruilian Xu, Guolin Zhong, Tanxiao Huang, Wan He, Cheng Kong, Xiaoni Zhang, Ying Wang, Ming Liu, Mingyan Xu, Shifu Chen
Lung cancer is the most commonly occurring type of cancer worldwide and also has the highest mortality rate. Although targeted therapy of non-small cell lung carcinoma (NSCLC) has become common, the majority of patients receiving first-line epithelial growth factor receptor (EGFR)-TKI treatment develop drug resistance. The EGFR T790M (NM_005228.4(EGFR):c.2369C>T (p.Thr790Met)) mutation accounts for half of all reported resistance cases; however, the molecular mechanism resulting in the drug resistance remains to be characterized...
March 2018: Oncology Letters
https://www.readbyqxmd.com/read/29547001/molecular-pathology-of-lung-cancer-cytology-specimens-a-concise-review
#18
Deepali Jain, Sinchita Roy-Chowdhuri
CONTEXT: - There has been a paradigm shift in the understanding of molecular pathogenesis of lung cancer. A number of oncogenic drivers have been identified in non-small cell lung carcinoma, such as the epidermal growth factor receptor ( EGFR) mutation and anaplastic lymphoma kinase ( ALK) gene rearrangement. Because of the clinical presentation at an advanced stage of disease in non-small cell lung carcinoma patients, the use of minimally invasive techniques is preferred to obtain a tumor sample for diagnosis...
March 16, 2018: Archives of Pathology & Laboratory Medicine
https://www.readbyqxmd.com/read/29546323/tumor-suppressive-effect-of-lrig1-a-negative-regulator-of-erbb-in-non-small-cell-lung-cancer-harboring-mutant-egfr
#19
Hidejiro Torigoe, Hiromasa Yamamoto, Masakiyo Sakaguchi, Chen Youyi, Kei Namba, Hiroki Sato, Kazuhiko Shien, Junichi Soh, Ken Suzawa, Shuta Tomida, Kazunori Tsukuda, Shinichiro Miyoshi, Shinichi Toyooka
Epidermal growth factor receptor (EGFR) is a member of the ErbB (HER) family that is known to play important roles in the pathogenesis of various human cancers. Mutations of the EGFR gene are commonly found as oncogenic driver mutations, and have been targeted for treatment in non-small cell lung cancer (NSCLC). Leucine-rich repeat and immunoglobulin-like domain protein-1 (LRIG1) is a cell-surface protein that is known as a negative regulator of the ErbB (HER) family. In this study, we first confirmed that the expression levels of LRIG1 were much lower in NSCLC than in non-malignant cells or tissues...
March 13, 2018: Carcinogenesis
https://www.readbyqxmd.com/read/29541205/monitoring-colorectal-cancer-following-surgery-using-plasma-circulating-tumor-dna
#20
Xiao Sun, Tanxiao Huang, Fangsheng Cheng, Kaibing Huang, Ming Liu, Wan He, Mingwei Li, Xiaoni Zhang, Mingyan Xu, Shifu Chen, Ligang Xia
Postoperative monitoring for patients with colorectal cancer (CRC) requires sensitive biomarkers that are associated with medical response and adjuvant therapy following surgery. Conventional tumor biomarkers [including carcinoembryonic antigen (CEA), CA19-9 and CA125] are widely used, but none of the markers provide high sensitivity or specificity. Previous studies indicated that circulating tumor DNA (ctDNA) is useful for postoperative monitoring of patients with cancer. However, the majority of previous studies involved patients with lung cancer, and therefore further studies are required which investigate patients with CRC...
April 2018: Oncology Letters
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